The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108142 https://doi.org/10.1523/ENEURO.0268-17.2017 |
Resumo: | Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cultured rat hippocampal neurons by stimulating BDNF-Trk signaling. Microarray experiments identified a large number of transcripts that are coimmunoprecipitated with hnRNP K, and about 60% of these transcripts are dissociated from the protein upon stimulation of rat hippocampal neurons with BDNF. In vivo studies also showed a role for TrkB signaling in the dissociation of transcripts from hnRNP K upon high-frequency stimulation (HFS) of medial perforant path-granule cell synapses of male rat dentate gyrus (DG). Furthermore, treatment of rat hippocampal synaptoneurosomes with BDNF decreased the coimmunoprecipitation of hnRNP K with mRNAs coding for glutamate receptor subunits, Ca2+- and calmodulin-dependent protein kinase IIβ (CaMKIIβ) and BDNF. Downregulation of hnRNP K impaired the BDNF-induced enhancement of NMDA receptor (NMDAR)-mediated mEPSC, and similar results were obtained upon inhibition of protein synthesis with cycloheximide. The results demonstrate that BDNF regulates specific populations of hnRNP-associated mRNAs in neuronal dendrites and suggests an important role of hnRNP K in BDNF-dependent forms of synaptic plasticity. |
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The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal NeuronsBDNFlocal translationlong-term synaptic potentiationneurotrophinsNMDA receptorsRNA transportAnimalsAnimals, Outbred StrainsBrain-Derived Neurotrophic FactorCells, CulturedDendritesExcitatory Postsynaptic PotentialsFemaleHEK293 CellsHeterogeneous-Nuclear Ribonucleoprotein KHippocampusHumansMaleMicroarray AnalysisMicroelectrodesRNA TransportRNA, MessengerRats, Sprague-DawleyRats, WistarReceptors, N-Methyl-D-AspartateSynapsesSynaptosomesBrain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cultured rat hippocampal neurons by stimulating BDNF-Trk signaling. Microarray experiments identified a large number of transcripts that are coimmunoprecipitated with hnRNP K, and about 60% of these transcripts are dissociated from the protein upon stimulation of rat hippocampal neurons with BDNF. In vivo studies also showed a role for TrkB signaling in the dissociation of transcripts from hnRNP K upon high-frequency stimulation (HFS) of medial perforant path-granule cell synapses of male rat dentate gyrus (DG). Furthermore, treatment of rat hippocampal synaptoneurosomes with BDNF decreased the coimmunoprecipitation of hnRNP K with mRNAs coding for glutamate receptor subunits, Ca2+- and calmodulin-dependent protein kinase IIβ (CaMKIIβ) and BDNF. Downregulation of hnRNP K impaired the BDNF-induced enhancement of NMDA receptor (NMDAR)-mediated mEPSC, and similar results were obtained upon inhibition of protein synthesis with cycloheximide. The results demonstrate that BDNF regulates specific populations of hnRNP-associated mRNAs in neuronal dendrites and suggests an important role of hnRNP K in BDNF-dependent forms of synaptic plasticity.Society for Neuroscience2017info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108142http://hdl.handle.net/10316/108142https://doi.org/10.1523/ENEURO.0268-17.2017eng2373-2822Leal, GracianoComprido, DiogoLuca, Pasqualino DeMorais, Eduardo Manuel FirmoRodrigues, LuísMele, MirandaSantos, Ana R.Costa, Rui O.Pinto, Maria JoanaPatil, SudarshanBerentsen, BirgitteAfonso, Pedro M.Carreto, LauraLi, Ka WanPinheiro, Paulo S.Almeida, Ramiro D.Santos, Manuel A. S.Bramham, Clive R.Duarte, Carlos B.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-13T17:10:16Zoai:estudogeral.uc.pt:10316/108142Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:26.277571Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
title |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
spellingShingle |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons Leal, Graciano BDNF local translation long-term synaptic potentiation neurotrophins NMDA receptors RNA transport Animals Animals, Outbred Strains Brain-Derived Neurotrophic Factor Cells, Cultured Dendrites Excitatory Postsynaptic Potentials Female HEK293 Cells Heterogeneous-Nuclear Ribonucleoprotein K Hippocampus Humans Male Microarray Analysis Microelectrodes RNA Transport RNA, Messenger Rats, Sprague-Dawley Rats, Wistar Receptors, N-Methyl-D-Aspartate Synapses Synaptosomes |
title_short |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
title_full |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
title_fullStr |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
title_full_unstemmed |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
title_sort |
The RNA-Binding Protein hnRNP K Mediates the Effect of BDNF on Dendritic mRNA Metabolism and Regulates Synaptic NMDA Receptors in Hippocampal Neurons |
author |
Leal, Graciano |
author_facet |
Leal, Graciano Comprido, Diogo Luca, Pasqualino De Morais, Eduardo Manuel Firmo Rodrigues, Luís Mele, Miranda Santos, Ana R. Costa, Rui O. Pinto, Maria Joana Patil, Sudarshan Berentsen, Birgitte Afonso, Pedro M. Carreto, Laura Li, Ka Wan Pinheiro, Paulo S. Almeida, Ramiro D. Santos, Manuel A. S. Bramham, Clive R. Duarte, Carlos B. |
author_role |
author |
author2 |
Comprido, Diogo Luca, Pasqualino De Morais, Eduardo Manuel Firmo Rodrigues, Luís Mele, Miranda Santos, Ana R. Costa, Rui O. Pinto, Maria Joana Patil, Sudarshan Berentsen, Birgitte Afonso, Pedro M. Carreto, Laura Li, Ka Wan Pinheiro, Paulo S. Almeida, Ramiro D. Santos, Manuel A. S. Bramham, Clive R. Duarte, Carlos B. |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Leal, Graciano Comprido, Diogo Luca, Pasqualino De Morais, Eduardo Manuel Firmo Rodrigues, Luís Mele, Miranda Santos, Ana R. Costa, Rui O. Pinto, Maria Joana Patil, Sudarshan Berentsen, Birgitte Afonso, Pedro M. Carreto, Laura Li, Ka Wan Pinheiro, Paulo S. Almeida, Ramiro D. Santos, Manuel A. S. Bramham, Clive R. Duarte, Carlos B. |
dc.subject.por.fl_str_mv |
BDNF local translation long-term synaptic potentiation neurotrophins NMDA receptors RNA transport Animals Animals, Outbred Strains Brain-Derived Neurotrophic Factor Cells, Cultured Dendrites Excitatory Postsynaptic Potentials Female HEK293 Cells Heterogeneous-Nuclear Ribonucleoprotein K Hippocampus Humans Male Microarray Analysis Microelectrodes RNA Transport RNA, Messenger Rats, Sprague-Dawley Rats, Wistar Receptors, N-Methyl-D-Aspartate Synapses Synaptosomes |
topic |
BDNF local translation long-term synaptic potentiation neurotrophins NMDA receptors RNA transport Animals Animals, Outbred Strains Brain-Derived Neurotrophic Factor Cells, Cultured Dendrites Excitatory Postsynaptic Potentials Female HEK293 Cells Heterogeneous-Nuclear Ribonucleoprotein K Hippocampus Humans Male Microarray Analysis Microelectrodes RNA Transport RNA, Messenger Rats, Sprague-Dawley Rats, Wistar Receptors, N-Methyl-D-Aspartate Synapses Synaptosomes |
description |
Brain-derived neurotrophic factor (BDNF) is an important mediator of long-term synaptic potentiation (LTP) in the hippocampus. The local effects of BDNF depend on the activation of translation activity, which requires the delivery of transcripts to the synapse. In this work, we found that neuronal activity regulates the dendritic localization of the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cultured rat hippocampal neurons by stimulating BDNF-Trk signaling. Microarray experiments identified a large number of transcripts that are coimmunoprecipitated with hnRNP K, and about 60% of these transcripts are dissociated from the protein upon stimulation of rat hippocampal neurons with BDNF. In vivo studies also showed a role for TrkB signaling in the dissociation of transcripts from hnRNP K upon high-frequency stimulation (HFS) of medial perforant path-granule cell synapses of male rat dentate gyrus (DG). Furthermore, treatment of rat hippocampal synaptoneurosomes with BDNF decreased the coimmunoprecipitation of hnRNP K with mRNAs coding for glutamate receptor subunits, Ca2+- and calmodulin-dependent protein kinase IIβ (CaMKIIβ) and BDNF. Downregulation of hnRNP K impaired the BDNF-induced enhancement of NMDA receptor (NMDAR)-mediated mEPSC, and similar results were obtained upon inhibition of protein synthesis with cycloheximide. The results demonstrate that BDNF regulates specific populations of hnRNP-associated mRNAs in neuronal dendrites and suggests an important role of hnRNP K in BDNF-dependent forms of synaptic plasticity. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108142 http://hdl.handle.net/10316/108142 https://doi.org/10.1523/ENEURO.0268-17.2017 |
url |
http://hdl.handle.net/10316/108142 https://doi.org/10.1523/ENEURO.0268-17.2017 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2373-2822 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Society for Neuroscience |
publisher.none.fl_str_mv |
Society for Neuroscience |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134129148657664 |